The proposed studies are designed to provide a molecular analysis of structure, organization and polymorphisms of genes within the major histocompatibility complex (MHC) on the short arm of human chromosome six (6p). The definition of functional domains and post synthetic modifications as revealed in primary structure of the MHC class III gene products will be elucidated. The findings from these two groups of studies will be applied to define molecular markers and mechanisms for the analysis of linkage to human congenital/genetic diseases such as ankylosing spondylitis, myasthenia gravis and deficiency of one of the class III proteins (C2). Modern tools of molecular genetics, protein biosynthesis and protein chemistry will be applied to the study of patients, their families and normal families with informative markers on 6p. The overall objectives are to understand the basis for 6p linked diseases, and to find predictive independent markers for these disorders. Thus, more effective and comprehensive genetic counselling might result.